OCALIVA: The Facts

Yes. OCALIVA, the most prescribed second-line PBC therapy in the US, continues to be available for the treatment of appropriate patients living with PBC, under the US Food & Drug Administration (FDA) Accelerated Approval Program.

PBC is a rare disease with limited treatment options.¹ OCALIVA works differently than other approved PBC treatments, and it is an established part of the treatment landscape.²

When FDA needs to consider a science, technology or policy question related to a medicine it is reviewing, it may ask a group of outside experts to meet and share their perspectives.³

In September 2024, FDA convened a Gastrointestinal Drugs Advisory Committee meeting to discuss Intercept's supplemental New Drug Application for OCALIVA. This application sought full FDA approval and to confirm OCALIVA's clinical benefits for adults with PBC.

For comprehensive information about FDA Advisory Committees, click here. For more information about the September 13, 2024, OCALIVA-related Advisory Committee meeting, click here.

The Advisory Committee focused its review on data from two studies: the randomized confirmatory COBALT trial (747-302) and the observational HEROES study (405). After presentations and testimony, the committee concluded that the data from these two studies did not confirm OCALIVA's clinical benefit and declined to endorse the medicine's risk-benefit profile for full approval.

Intercept noted at the meeting that the totality of evidence for OCALIVA extends beyond these two studies and includes:

• Evidence from additional clinical trials^4,5
• Observational studies and external-control analyses comparing OCALIVA treatment outcomes to established PBC registry data^6,7,8
• More than eight years of patient treatment experience spanning more than 42,000 cumulative patient years of exposure (as of June 2025, more than nine years and 53,000 cumulative patient years of exposure)

Full details pertaining to this Advisory Committee Meeting can be accessed here.

In November 2024, FDA issued a Complete Response Letter declining to grant full approval for OCALIVA based on the reviewed supplemental New Drug Application. However, OCALIVA remains available for appropriate patients under FDA accelerated approval.

All three FDA-approved second-line treatment options for people with PBC in the US, including OCALIVA, are currently approved under the accelerated approval pathway.

A Drug Safety Communication (DSC) is a way FDA informs healthcare professionals and patients about potential safety considerations for a prescription medicine.

FDA issued the DSC following its review of the supplemental New Drug Application that Intercept submitted seeking full approval for OCALIVA. In the DSC, FDA said in reviewing the confirmatory clinical study, which was required as part of the supplemental New Drug Application, it identified cases of serious liver events that occurred among some OCALIVA-treated participants without cirrhosis (a condition in which the liver is scarred and permanently damaged).

To assess this potential risk, FDA has opened a Newly Identified Safety Signal (NISS) evaluation regarding OCALIVA and liver disorder.

The opening of a NISS does not mean that FDA has identified a causal relationship between the potential safety risk and the medicine being assessed. In addition, FDA has stated that its identification of a potential new safety signal with respect to a medicine does not mean that healthcare providers should not prescribe it or that patients should stop taking it while an evaluation is being conducted. FDA suggests that people who have questions about their use of the identified medicine should contact their health care provider.

FDA also said in the DSC that post-market safety monitoring identified three cases of liver-related events among patients for whom OCALIVA should have been discontinued based on progression of their liver disease as indicated in the current OCALIVA US Prescribing Information (USPI). The DSC emphasized the need for frequent liver-test monitoring and therapy discontinuation if liver disease progresses. These recommendations are consistent with OCALIVA's USPI.

The full DSC issued by FDA can be found here.

Patients are our priority.

Intercept recently conducted a comprehensive review of its clinical-trial and post-marketing safety data regarding OCALIVA and liver disorder. The results of Intercept's safety analysis did not find evidence of a new safety signal regarding OCALIVA and liver disorder in the current US Prescribing Information (USPI) patient population. Intercept reviewed its analysis and findings with a panel of third-party experts who agreed with the Company's conclusion. This information has been shared with FDA, which is continuing to evaluate the safety observations noted in the December 2024 DSC.

In addition to the recently conducted analysis, Intercept continuously monitors OCALIVA's safety profile and conducts regular reviews of adverse-event reports. The safety data available to Intercept reinforces the Company's position that OCALIVA has a favorable benefit-risk profile for appropriate patients when prescribed in accordance with the USPI.

Because PBC is a progressive liver disease, it is important for healthcare professionals to take an individualized approach to benefit risk assessment when they select a treatment option for each patient.⁹

Intercept reiterates the importance of patients and healthcare professionals adhering to the USPI and patient Medication Guide, and routinely monitoring PBC patients taking OCALIVA for biochemical response, worsening of liver function, tolerability and progression of PBC.

Intercept continuously monitors OCALIVA's safety profile and conducts regular reviews of adverse-event reports.

Prescribing guidelines in the US Prescribing Information (USPI) and Patient Medication Guide outline the appropriate patient population and monitoring requirements. Consistent with standard clinical practice and the OCALIVA USPI, all people taking OCALIVA should be routinely monitored for biochemical response, worsening of liver function, tolerability and progression of PBC. Additionally, published clinical practice guidance recommends performing liver tests at three to six-month intervals, regardless of treatment.¹⁰

The majority of people taking OCALIVA enroll in Interconnect Support Services, an Intercept patient support program that requires healthcare providers to attest that patients who are prescribed OCALIVA do not have contraindications to its use.

People taking OCALIVA should discuss any questions or concerns with their healthcare provider. Healthcare professionals who have questions about OCALIVA should contact Intercept Medical Information.

Intercept has had constructive engagement with FDA. The Company has proposed a new confirmatory trial design incorporating input from clinical experts, regulatory specialists, statisticians, trial designers, and patient advocacy groups.

Reports of serious liver events among patients being treated with OCALIVA have been reported, particularly among those patients with liver cirrhosis. Some of the cases involved reports of liver transplants and death.

Reports of serious liver events have significantly decreased since the medicine's US Prescribing Information (USPI) was substantially updated in 2021. Patients should not take OCALIVA if they have PBC with liver cirrhosis with symptoms such as fluid in the stomach-area or confusion (decompensated liver cirrhosis) or with abnormalities in certain liver monitoring tests; or have a complete blockage of the bile ducts in their liver or gallbladder.

As stated in the December 2024 Drug Safety Communication, prescribers should use OCALIVA in line with its USPI; prescribers and patients should engage in frequent liver test monitoring, look for signs of liver injury or decreased liver function, and discontinue treatment with OCALIVA if contraindicated.

See below for detailed information pertaining to the OCALIVA Indication and Important Safety Information.